Na⁺ transport in the normal and failing heart - remember the balance

In the heart, intracellular Na(+) concentration ([Na(+)]i) is a key modulator of Ca(2+) cycling, contractility and cardiac myocyte metabolism. Several Na(+) transporters are electrogenic, thus they both contribute to shaping the cardiac action potential and at the same time are affected by it. [Na(+)]i is controlled by the balance between Na(+) influx through various pathways, including the Na(+)/Ca(2+) exchanger and Na(+) channels, and Na(+) extrusion via the Na(+)/K(+)-ATPase. [Na(+)]i is elevated in HF due to a combination of increased entry through Na(+) channels and/or Na(+)/H(+) exchanger and reduced activity of the Na(+)/K(+)-ATPase. Here we review the major Na(+) transport pathways in cardiac myocytes and how they participate in regulating [Na(+)]i in normal and failing hearts. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes."